Stephen Wren

Title : Discovery of novel inhibitors of P300/CBP-associated factor (PCAF)

Abstract:

The Alzheimer’s Research UK Oxford Drug Discovery Institute combines the deep disease knowledge and biology expertise of Oxford University with high quality, innovative drug discovery technologies and expertise to identify new ways of treating neurodegeneration. Our capabilities directed towards the creation of lead compounds for neurodegenerative targets will be presented along with our ability to progress successful candidates through the drug discovery pipeline towards commercialisation. One of our projects involves the development of novel PCAF inhibitors with the aim to inhibit neuroinflammatory pathways in Alzheimer’s disease through the modulation of histone acetylation of key inflammatory genes. PCAF inhibition is expected to decrease neuroinflammation by regulation of NF-kB acetylation. We will present our efforts to delineate which functional domain (histone acetyl transferase or bromodomain) of PCAF is most important to target for efficacy versus neuroinflammation.

Audience take away:

• The audience will become aware of the Alzheimer’s Research UK Oxford Drug Discovery Institute’s activities and focus.
• How the Structural Genomics Consortium, Oxford, is working together with the Alzheimer’s Research UK Oxford Drug Discovery Institute to discover new PCAF inhibitors.
• The audience will be introduced to targeting neuroinflammation as a new modality for treatment of dementia.

Biography:

Stephen Wren obtained his PhD in Organic Chemistry from Cambridge University. He is highly experienced in medicinal chemistry and has worked on a diverse set of biological targets over many disease areas in several organisations. For examples, he helped to lead the chemistry effort directed towards the identification of SMTC1100 (Summit’s Duchenne Muscular Dystrophy drug), currently undergoing clinical evaluation. Direct experience of CNS research was gained when Stephen guided a team in support of a lead optimisation project for Lundbeck (during his time at Argenta Discovery). In this role, he acted as project leader for the discovery of novel glycine transporter 1 inhibitors for the treatment of schizophrenia. These studies resulted in the identification of a development candidate. Stephen joined Prof. Paul Brennan’s Group at the Oxford Drug Discovery Institute in June 2015 to work on Alzheimer’s drug discovery.